Antibiotic resistance is a global crisis with few solutions on the horizon [1]. In the United States, resistant infections account for over 2,000,000 illnesses each year with methicillin-resistant Staphylococcus aureus (MRSA) responsible for over 11,000 deaths per year [2]. Despite the severity of the problem, there are few new molecules nearing approval [3] illustrating the need for new antibiotic discovery platforms [4].
Antimicrobial peptides (AMPs) have often been proposed as new antibiotics and many are in clinical development [5]. While the in vivo behavior of AMPs is often poor, there have been a number of peptides that demonstrate efficacy including short peptide mimetics [6].
Another antibacterial strategy is to develop agents that sensitize resistant bacteria to approved antibiotics. There have a number of agents reported that sensitize MRSA to beta-lactam (β-lactam) antibiotics. These include small molecules [7-11], peptides [12], peptide mimetics [13], and a human milk protein complex [14].
Accordingly, there remains a need in the art for improved methods and compositions for treating MRSA infections and for sensitizing MRSA to beta-lactam antibiotics.